Dataset Information

Whole Exome Sequencing Study Identifies Novel Rare Risk Variants for Habitual Coffee Consumption Involved in Olfactory Receptor and Hyperphagia.

ABSTRACT: Habitual coffee consumption is an addictive behavior with unknown genetic variations and has raised public health issues about its potential health-related outcomes. We performed exome-wide association studies to identify rare risk variants contributing to habitual coffee consumption utilizing the newly released UK Biobank exome dataset (n = 200,643). A total of 34,761 qualifying variants were imported into SKAT to conduct gene-based burden and robust tests with minor allele frequency <0.01, adjusting the polygenic risk scores (PRS) of coffee intake to exclude the effect of common coffee-related polygenic risk. The gene-based burden and robust test of the exonic variants found seven exome-wide significant associations, such as OR2G2 (P_SKAT = 1.88 × 10^-9, P_SKAT-Robust = 2.91 × 10^-17), VEZT1 (P_SKAT = 3.72 × 10^-7, P_SKAT-Robust = 1.41 × 10^-7), and IRGC (P_SKAT = 2.92 × 10^-5, P_SKAT-Robust = 1.07 × 10^-7). These candidate genes were verified in the GWAS summary data of coffee intake, such as rs12737801 (p = 0.002) in OR2G2, and rs34439296 (p = 0.008) in IRGC. This study could help to extend genetic insights into the pathogenesis of coffee addiction, and may point to molecular mechanisms underlying health effects of habitual coffee consumption.

SUBMITTER: Cheng B

PROVIDER: S-EPMC9607528 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Whole Exome Sequencing Study Identifies Novel Rare Risk Variants for Habitual Coffee Consumption Involved in Olfactory Receptor and Hyperphagia.

Cheng Bolun B Pan Chuyu C Cheng Shiqiang S Meng Peilin P Liu Li L Wei Wenming W Yang Xuena X Jia Yumeng Y Wen Yan Y Zhang Feng F

Nutrients 20221016 20

Habitual coffee consumption is an addictive behavior with unknown genetic variations and has raised public health issues about its potential health-related outcomes. We performed exome-wide association studies to identify rare risk variants contributing to habitual coffee consumption utilizing the newly released UK Biobank exome dataset (n = 200,643). A total of 34,761 qualifying variants were imported into SKAT to conduct gene-based burden and robust tests with minor allele frequency <0.01, adj ...[more]

PMID: 36297015

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Project description:BackgroundCoffee intake may be inversely associated with colorectal cancer; however, previous studies have been inconsistent. Serum coffee metabolites are integrated exposure measures that may clarify associations with cancer and elucidate underlying mechanisms.ObjectivesOur aims were 2-fold as follows: 1) to identify serum metabolites associated with coffee intake and 2) to examine these metabolites in relation to colorectal cancer.DesignIn a nested case-control study of 251 colorectal cancer cases and 247 matched control subjects from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we conducted untargeted metabolomics analyses of baseline serum by using ultrahigh-performance liquid-phase chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Usual coffee intake was self-reported in a food-frequency questionnaire. We used partial Pearson correlations and linear regression to identify serum metabolites associated with coffee intake and conditional logistic regression to evaluate associations between coffee metabolites and colorectal cancer.ResultsAfter Bonferroni correction for multiple comparisons (P = 0.05 ÷ 657 metabolites), 29 serum metabolites were positively correlated with coffee intake (partial correlation coefficients: 0.18-0.61; P < 7.61 × 10(-5)); serum metabolites most highly correlated with coffee intake (partial correlation coefficients >0.40) included trigonelline (N'-methylnicotinate), quinate, and 7 unknown metabolites. Of 29 serum metabolites, 8 metabolites were directly related to caffeine metabolism, and 3 of these metabolites, theophylline (OR for 90th compared with 10th percentiles: 0.44; 95% CI: 0.25, 0.79; P-linear trend = 0.006), caffeine (OR for 90th compared with 10th percentiles: 0.56; 95% CI: 0.35, 0.89; P-linear trend = 0.015), and paraxanthine (OR for 90th compared with 10th percentiles: 0.58; 95% CI: 0.36, 0.94; P-linear trend = 0.027), were inversely associated with colorectal cancer.ConclusionsSerum metabolites can distinguish coffee drinkers from nondrinkers; some caffeine-related metabolites were inversely associated with colorectal cancer and should be studied further to clarify the role of coffee in the cause of colorectal cancer. The Prostate, Lung, Colorectal, and Ovarian trial was registered at clinicaltrials.gov as NCT00002540.

Dataset Information

Whole Exome Sequencing Study Identifies Novel Rare Risk Variants for Habitual Coffee Consumption Involved in Olfactory Receptor and Hyperphagia.

Publications

Whole Exome Sequencing Study Identifies Novel Rare Risk Variants for Habitual Coffee Consumption Involved in Olfactory Receptor and Hyperphagia.

Similar Datasets

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